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  #1  
Old 11-29-2017, 11:34 PM
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Default Marijuana: What causes the high?

Hello all,

I would like to know what exactly is causing the psychoactive effects of delta(9)-THC when using cannabis?

I know that delta(9)-THC may discriminate anandamide signaling by acting as a competitive CB1 agonist, but the mecanism which produces the "high" could not be specific to delta(9)-THC alone, any may implicate dopaminergic modulation of anandamide signaling: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834964/

What do you think?

tk
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Old 12-02-2017, 01:34 PM
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Any ideas??

Is delta(9)-THC acting as a reversible or irreversible dopamine agonist??
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Old 12-03-2017, 05:35 AM
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Cannabinoids work because they are analogs of human endocrine system compounds that act on cannabinoid receptors. THC works on CB1 receptors to induce anandamide and 2-arachidonoylglycerol, and that is what causes the high. THC alone will get you high, but it is a twitchy high that is not that great. THC is an agonist of both CB1 and CB2 receptors, but has a higher affinity for CB1. CBD doesn’t bind directly to either of the CB receptors, but blocks them. So CBD competes with and thus softens the THC high, as it were. CBD also interacts with other receptors, such as 5-HT1A receptors, which are linked to serotonin regulation, and the vanilloid receptor TRPV1, which functions as an ion channel.

It is not clearly understood how the addictive or reward process works for THC. Here is a study that was published in 2011 on it though:

The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys | Journal of Neuroscience
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Old 12-03-2017, 01:50 PM
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Quote:
Originally Posted by Big Sur View Post
Cannabinoids work because they are analogs of human endocrine system compounds that act on cannabinoid receptors. THC works on CB1 receptors to induce anandamide and 2-arachidonoylglycerol, and that is what causes the high. THC alone will get you high, but it is a twitchy high that is not that great. THC is an agonist of both CB1 and CB2 receptors, but has a higher affinity for CB1. CBD doesn’t bind directly to either of the CB receptors, but blocks them. So CBD competes with and thus softens the THC high, as it were. CBD also interacts with other receptors, such as 5-HT1A receptors, which are linked to serotonin regulation, and the vanilloid receptor TRPV1, which functions as an ion channel.

It is not clearly understood how the addictive or reward process works for THC. Here is a study that was published in 2011 on it though:

The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys | Journal of Neuroscience
Thanks for sharing B. I'll read that article for sure.
You really believe that delta(9)-THC induce endocannabinoid signaling?
I was thinking that a long time ago, and changed my mind since then.
In specific, it is widely accepted that delta(9)-THC exposure may selectively downregulate retrograde signaling by activating CB1 receptors.
Chronic downregulation of the endocannabinoid system is a good method to effectively restore dopamine activity.

Peace,

tk
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Old 12-04-2017, 12:49 AM
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Quote:
Originally Posted by tkadm30 View Post
Thanks for sharing B. I'll read that article for sure.
You really believe that delta(9)-THC induce endocannabinoid signaling?
Yes, but I believe that there are multiple processes going on, depending on the various levels of cannabinoids in weed. THC has at least one active metabolite, 11-Hydroxy-THC, which may play a direct role in the effects of weed on the brain. The devil is in the details though. Mammals react differently to different cannabinoids, and human phytocannabinoid research is sadly and severely lacking. Thanks to Emperor Nixon making Mj a schedule 1 narcotic.

Here is another page that has good information. They say that cannabinoids open the opioid pathway, by some "unknown mechanism".

https://www.edinformatics.com/intera...s/info/thc.htm

Specifically:

In addition, it has been shown that cannabinoids, through an unknown mechanism, activate endogenous opioid pathways via the µ1 opioid receptor, precipitating a dopamine release in the nucleus accumbens. The effects of the drug can be suppressed by the CB1 cannabinoid receptor antagonist rimonabant (SR141716A) or, interesting to note, the opioid receptor antagonists (opioid blockers) naloxone and naloxonazine.[3]

The mechanism of endocannabinoid synaptic transmission is understood by the following events: An excitatory transmission of the neurotransmitter glutamate causes an influx of calcium ions into the post-synaptic neuron. Through a mechanism not yet fully understood, the presence of calcium post-synaptically induces the production of endocannabinoids in the post-synaptic neuron. These endocannabinoids (such as anandamide) are released into the synaptic cleft. Once in the synaptic cleft, binding occurs at cannabinoid receptors present in pre-synaptic neurons where they can then modulate neurotransmission pre-synaptically. This form of neurotransmission is termed retrograde transmission, as the signal is carried in the opposite direction of orthodox propagation; it provides an interesting insight into neurotransmission, which previously was thought to be exclusively one way.
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Old 12-04-2017, 05:13 PM
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I believe it's a bit like opiates we have opioid receptors and cannabinoids receptors you take either drug the receptors are opened giving you a high. Completely different receptors of course giving a completely different high.
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Old 12-04-2017, 09:16 PM
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Quote:
Originally Posted by Big Sur View Post
The mechanism of endocannabinoid synaptic transmission is understood by the following events: An excitatory transmission of the neurotransmitter glutamate causes an influx of calcium ions into the post-synaptic neuron. Through a mechanism not yet fully understood, the presence of calcium post-synaptically induces the production of endocannabinoids in the post-synaptic neuron.
That extraordinary claim is not supported by a citation from a peer-reviewed study!
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Old 01-04-2018, 09:13 AM
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Do the activity of presynaptic calcium channel inhibit the release of endocannabinoids in the post-synaptic neuron?

See: https://www.ncbi.nlm.nih.gov/pubmed/24899717
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  #9  
Old 02-21-2018, 04:52 AM
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Default Hi Everyone

I would like to know that does CBD gummies get us high?
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  #10  
Old 02-21-2018, 10:15 AM
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Quote:
Originally Posted by farmacybliss View Post
I would like to know that does CBD gummies get us high?
CBD is not psychoactive so it cannot get you high.

CBD is also a potential antipsychotic, unlike delta(9)-THC, which directly binds to cannabinoid receptors (CB1/CB2) in the brain.

tk
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